Movement Effects on the Flow Physics and Nutrient Delivery in Engineered Valvular Tissues

Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering (HVTE) owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by steady flow and scaffold flexure play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). In addition, scaffold flexure may enhance nutrient (e.g. oxygen, glucose) transport. In this study, we computationally quantified the i) magnitude of fluid-induced shear stresses; ii) the extent of temporal fluid oscillations in the flow field using the oscillatory shear index (OSI) parameter, and iii) glucose and oxygen mass transport profiles. Noting that sample cyclic flexure induces a high degree of oscillatory shear stress (OSS), we incorporated moving boundary computational fluid dynamic simulations of samples housed within a bioreactor to consider the effects of: 1) no flow, no flexure (control group), 2) steady flow-alone, 3) cyclic flexure-alone and 4) combined steady flow and cyclic flexure environments. We also coupled a diffusion and convention mass transport equation to the simulated system. We found that the coexistence of both OSS and appreciable shear stress magnitudes, described by the newly introduced parameter OSI-t , explained the high levels of engineered collagen previously observed from combining cyclic flexure and steady flow states. On the other hand, each of these metrics on its own showed no association. This finding suggests that cyclic flexure and steady flow synergistically promote engineered heart valve tissue production via OSS, so long as the oscillations are accompanied by a critical magnitude of shear stress. In addition, our simulations showed that mass transport of glucose and oxygen is enhanced by sample movement at low sample porosities, but did not play a role in highly porous scaffolds. Preliminary in-house in vitro experiments showed that cell proliferation and phenotype is enhanced in OSI-t environments.

Processing of highly porous titanium parts by metal injection moulding in combination with innovative plasma treatment

A combinação da Moldagem por Injeção de pós Metálicos (Metal Injection Moulding MIM) e o Método do Retentor Espacial (Space Holder Method - SHM) é uma técnica promissora para fabricação de peças porosas de titânio com porosidade bem definida como implantes biomédicos, uma vez que permite um alto grau de automatização e redução dos custos de produção em larga escala quando comparado a técnica tradicional (SHM e usinagem a verde). Contudo a aplicação desta técnica é limitada pelo fato que há o fechamento parcial da porosidade na superfície das amostras, levando ao deterioramento da fixação do implante ao osso. E além disso, até o presente momento não foi possível atingir condições de processamento estáveis quando a quantidade de retentor espacial excede 50 vol. %. Entretanto, a literatura descreve que a melhor faixa de porosidade para implantes de titânio para coluna vertebral está entre 60 - 65 vol. %. Portanto, no presente estudo, duas abordagens foram conduzidas visando a produção de amostras altamente porosas através da combinação de MIM e SHM com o valor constante de retentor espacial de 70 vol. % e uma porosidade aberta na superfície. Na primeira abordagem, a quantidade ótima de retentor espacial foi investigada, para tal foram melhorados a homogeneização do feedstock e os parâmetros de processo com o propósito de permitir a injeção do feedstock. Na segunda abordagem, tratamento por plasma foi aplicado nas amostras antes da etapa final de sinterização. Ambas rotas resultaram na melhoria da estabilidade dimensional das amostras durante a extração térmica do ligante e sinterização, permitindo a sinterização de amostras de titânio altamente porosas sem deformação da estrutura.

Gas-cushioned droplet impacts with a thin layer of porous media

Peer reviewed

Gas-cushioned droplet impacts with a thin layer of porous media

Peer reviewed

A Force-Balanced Control Volume Finite Element Method for Multi-Phase Porous Media Flow Modelling

Peer reviewed

Newly-developed parameters to quantify texture : application to polymeric porous structures

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Simultaneous observation of current oscillations and porous film growth during anodization of InP

The observation of spontaneous oscillations in current during the anodization of InP in relatively high concentrations of KOH electrolytes is reported. Oscillations were observed under potential sweep and constant potential conditions. Well-defined oscillations are observed during linear potential sweeps of InP in 5 mol dm-3 KOH to potentials above ∼1.7 V (SCE) at scan rates in the range of 50 to 500 mV s-1. The oscillations observed exhibit an asymmetrical current versus potential profile, and the charge per cycle was found to increase linearly with potential. More complex oscillatory behavior was observed under constant potential conditions. Periodic damped oscillations are observed in high concentrations of electrolyte whereas undamped sinusoidal oscillations are observed in relatively lower concentrations. In both cases, the anodization of InP results in porous InP formation, and the current in the oscillatory region corresponds to the cyclical effective area changes due to pitting dissolution of the InP surface with the coincidental growth of a thick porous In2O3 film.

Anodic behavior of InP: film growth, porous structures and current oscillations.

We review our recent work on the anodization of InP in KOH electrolytes. The anodic oxidation processes are shown to be remarkably different in different concentrations of KOH. Anodization in 2 - 5 mol dm-3 KOH electrolytes results in the formation of porous InP layers but, under similar conditions in a 1 mol dm-3 KOH, no porous structure is evident. Rather, the InP electrode is covered with a thin, compact surface film at lower potentials and, at higher potentials, a highly porous surface film is formed which cracks on drying. Anodization of electrodes in 2 - 5 mol dm-3 KOH results in the formation of porous InP under both potential sweep and constant potential conditions. The porosity is estimated at ~65%. A thin layer (~ 30 nm) close to the surface appears to be unmodified. It is observed that this dense, near-surface layer is penetrated by a low density of pores which appear to connected it to the electrolyte. Well-defined oscillations are observed when InP is anodized in both the KOH and (NH4)2S. The charge per cycle remains constant at 0.32 C cm-2 in (NH4)2S but increases linearly with potential in KOH. Although the characteristics of the oscillations in the two systems differ, both show reproducible and well-behaved values of charge per cycle.

Pitting and porous layer formation on n-InP anodes

Surface pitting occurs when InP electrodes are anodized in KOH electrolytes at concentrations in the range 2 - 5 mol dm-3. The process has been investigated using atomic force microscopy (AFM) and the results correlated with cross-sectional transmission electron microscopy (TEM) and electroanalytical measurements. AFM measurements show that pitting of the surface occurs and the density of pits is observed to increase with time under both potentiodynamic and potentiostatic conditions. This indicates a progressive pit nucleation process and implies that the development of porous domains beneath the surface is also progressive in nature. Evidence for this is seen in plan view TEM images in which individual domains are seen to be at different stages of development. Analysis of the cyclic voltammograms of InP electrodes in 5 mol dm-3 KOH indicates that, above a critical potential for pit formation, the anodic current is predominantly time dependent and there is little differential dependence of the current on potential. Thus, pores continue to grow with time when the potential is high enough to maintain depletion layer breakdown conditions.

Formation and characterization of porous InP layers in KOH Solutions

Porous InP layers were formed electrochemically on (100) oriented n-InP substrates in various concentrations of aqueous KOH under dark conditions. In KOH concentrations from 2 mol dm-3 to 5 mol dm-3, a porous layer is obtained underneath a dense near-surface layer. The pores within the porous layer appear to propagate from holes through the near-surface layer. Transmission electron microscopy studies of the porous layers formed under both potentiodynamic and potentiostatic conditions show that both the thickness of the porous layer and the mean pore diameter decrease with increasing KOH concentration. The degree of porosity, estimated to be 65%, was found to remain relatively constant for all the porous layers studied.

Scaffold-free, Human Mesenchymal Stem Cell-Based Tissue Engineered Blood Vessels.

Tissue-engineered blood vessels (TEBV) can serve as vascular grafts and may also play an important role in the development of organs-on-a-chip. Most TEBV construction involves scaffolding with biomaterials such as collagen gel or electrospun fibrous mesh. Hypothesizing that a scaffold-free TEBV may be advantageous, we constructed a tubular structure (1 mm i.d.) from aligned human mesenchymal cell sheets (hMSC) as the wall and human endothelial progenitor cell (hEPC) coating as the lumen. The burst pressure of the scaffold-free TEBV was above 200 mmHg after three weeks of sequential culture in a rotating wall bioreactor and perfusion at 6.8 dynes/cm(2). The interwoven organization of the cell layers and extensive extracellular matrix (ECM) formation of the hMSC-based TEBV resembled that of native blood vessels. The TEBV exhibited flow-mediated vasodilation, vasoconstriction after exposure to 1 μM phenylephrine and released nitric oxide in a manner similar to that of porcine femoral vein. HL-60 cells attached to the TEBV lumen after TNF-α activation to suggest a functional endothelium. This study demonstrates the potential of a hEPC endothelialized hMSC-based TEBV for drug screening.

Evaluation of a gelatin modified poly(ɛ-caprolactone) film as a scaffold for lung disease

Lung transplantation is a necessary step for the patients with the end-stage of chronic obstructive pulmonary disease. The use of artificial lungs is a promising alternative to natural lung transplantation which is complicated and is restricted by low organ donations. For successful lung engineering, it is important to choose the correct combination of specific biological cells and a synthetic carrier polymer. The focus of this study was to investigate the interactions of human lung epithelial cell line NCl-H292 that is involved in lung tissue development with the biodegradable poly(ϵ-caprolactone) before and after its chemical modification to evaluate potential for use in artificial lung formation. Also, the effect of polymer chemical modification on its mechanical and surface properties has been investigated. The poly(ϵ-caprolactone) surface was modified using aminolysis followed by immobilization of gelatine. The unmodified and modified polymer surfaces were characterized for roughness, tensile strength, and NCl-H292 metabolic cell activity. The results showed for the first time the possibility for NCI-H292 cells to adhere on this polymeric material. The Resazurin assay showed that the metabolic activity at 24 hours post seeding of 80% in the presence of the unmodified and greater than 100% in the presence of the modified polymer was observed. The roughness of the poly(ϵ-caprolactone) increased from 4 nm to 26 nm and the film strength increased from 0.01 kN to 0.045 kN when the material was chemically modified. The results obtained to date show potential for using modified poly(ϵ-caprolactone) as a scaffold for lung tissue engineering.

Newly-developed parameters to quantify texture : application to polymeric porous structures

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Porous Materials with Tunable Structure and Mechanical Properties via Templated Layer-by-Layer Assembly

The deposition of stiff and strong coatings onto porous templates offers a novel strategy for fabricating macroscale materials with controlled architectures at the micro- and nanoscale. Here, layer-by-layer assembly is utilized to fabricate nanocomposite-coated foams with highly customizable properties by depositing polymer–nanoclay coatings onto open-cell foam templates. The compressive mechanical behavior of these materials evolves in a predictable manner that is qualitatively captured by scaling laws for the mechanical properties of cellular materials. The observed and predicted properties span a remarkable range of density-stiffness space, extending from regions of very soft elastomer foams to very stiff, lightweight honeycomb and lattice materials.